Histone deacetylase HDAC (histone) is a kind of protease, which plays an important role in the structural modification and regulation of gene expression. Under normal circumstances, the acetylation of histone is suitable for DNA and histone octamer dissociated, nucleosome structure relaxation, so that a variety of transcription factors and synergistic transcription factors to DNA binding site specificity combined activation of gene transcription. In the nucleus, histone acetylation and histone to acetylation process is in a dynamic balance, and the histone acetyl transfer enzymes (histone acetyltransferase, hat) and histone deacetylases (histone deacetylase, HDAC) common regulation.
Histone acetylation modification plays an important role in the occurrence and development of tumor. In the normal cell body, once there is an imbalance between the acetylation of histone and histone acetylation, which'd leads to the change of normal cell cycle and cell metabolism behavior and induce tumors accordingly. Histone to acetylation enzyme catalyzed by histone deacetylation, maintain histone acetylation and de acetylation state of equilibrium, many processes and cancer related gene expression, cell proliferation, differentiation and apoptosis is closely related. In cancer cells, HDAC overexpression leads to the enhancement of acetylation and histone through a return to positive charge, thereby increasing the gravitational force between DNA and histone, the relaxation of the nucleosome becomes very closely, is not conducive to the specific gene expression, including several tumor suppressor genes.
With the further development of life science, molecular biology research on the pathogenesis and mechanism of tumor has provided the basis for the development of anti-tumor drugs with low toxicity and high efficiency. Histone deacetylases (HDACs) is one of the key enzymes for the maintenance of chromosomal basic composition unit of the nucleosome organization protein acetylation balance, the catalyzed by histone acetylation, and transcriptional repressor of genes that are closely related, involved in promoting gene silencing of many processes is a hot target for anticancer drug design. Histone deacetylase inhibitors (HDACi) can increase acetylation of protein in a specific region of chromatin histone acetylation, thereby regulating the expression and stability of apoptosis and differentiation-related protein, induction of apoptosis and differentiation, become a new class of anticancer drugs. HDACi not only have a good therapeutic effect against a variety of hematological malignancies and solid tumors, but also has a relatively high selectivity and low toxicity advantages of tumor cells.